The Picornaviridae represents a very large family of small RNA viruses responsible for many serious human and animal diseases (Strauss and Strauss 2002). The Picornaviridae include four major genera: Enterovirus, Rhinovirus, Apthovirus and Hepatovirus. The Enterovirus genus includes polioviruses, coxsackieviruses, echoviruses, and enteroviruses.
Poliovirus is the etiologic agent of the disease poliomyelitis in humans, and there are three known serotypes of the virus. The oral poliovaccine, typically given to children, is a mixture of the Sabin strain of the virus. The oral poliovirus vaccine is safe and effective, yet has two limitations. First, the vaccine is unstable since current vaccines are inactivated by relatively brief (less than 24 hours) exposure to temperatures of 37° C. This necessitates transport in a frozen state to the locale where they are administered. Second, the vaccine occasionally reverts to virulence in vaccine recipients and the reverted virulent virus may then be passed to other individuals who come into contact with the recipient in whom the vaccine has reverted.
The human rhinoviruses consist of at least 100 serotypes and are the primary causative agents of the common cold. Because of the large number of serotypes, development of a vaccine is problematic and antiviral agents may therefore be the best approach to treatment. The Coxsackie viruses and other human enteroviruses (multiple serotypes), are associated with a wide range of human diseases including summer flus, diarrhea, meningitis, hepatitis, pneumonia, myocarditis, pericarditis, and diabetes. These infections occur sporadically in the general population, but are becoming more common among children in day care and their parents and siblings. Other important members of the Picornaviridae family include human hepatitis A virus, Theiler's murine encephalomyelitis virus, foot-and-mouth disease virus, and mengovirus.
The existing drugs which are used against the viruses described above are only moderately effective, and are typically effective against only a limited subset of the rhinovirus serotypes. In general, the available drugs have either failed to demonstrate sufficient prophylactic effects or are converted in the body into inactive metabolites.
Thus, there remains a need for a more effective antiviral therapy in several members of the Picornoviridae family.